scholarly journals Effect of high cut-off dialysis for acute kidney injury secondary to cast nephropathy in patients with multiple myeloma: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Blanca Tarragón ◽  
Nan Ye ◽  
Martin Gallagher ◽  
Shaundeep Sen ◽  
Jose Maria Portolés ◽  
...  

ABSTRACT Background Acute kidney injury (AKI) caused by cast nephropathy is associated with increased morbidity and mortality among patients with multiple myeloma (MM). High cut-off haemodialysis (HCO-HD) has proven to be effective in the removal of serum light chains but the effect on clinical outcomes, especially renal recovery, remains uncertain. Methods A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) and observational studies (OBSs) assessing the effect of HCO-HD on clinical outcomes of patients with MM complicated by cast nephropathy–induced severe AKI. The primary outcome was all-cause mortality at the end of the study. The secondary outcomes included all-cause mortality at 12 months, HD independence and serum kappa and lambda light chain reduction. Pooled analysis was performed using random effects models. Results We identified five studies, comprising two RCTs and three retrospective cohort studies, including 276 patients with a mean follow-up of 18.7 months. The majority of the studies were of suboptimal quality and underpowered. Compared with patients treated with conventional HD, HCO-HD was not associated with a survival benefit at 12 months {five studies, 276 patients, relative risk [RR] 1.02 [95% confidence interval (CI) 0.76–1.35], I2 = 33.9%} or at the end of the studies at an average of 34 months [five studies, 276 patients, RR 1.32 (95% CI 0.71–2.45), I2 = 62.0%]. There was no difference in HD independence at 90 days [two trials, 78 patients, RR 2.23 (95% CI 1.09–4.55)], 6 months [two studies, 188 patients, RR 1.19 (95% CI 0.68–2.06)] or 12 months [two studies, 188 patients, RR 1.14 (95% CI 0.58–2.26)]. Patients receiving HCO dialysis, however, had a greater reduction in serum kappa [two studies, 188 patients, weighted mean difference (WMD) 46.7 (95% CI 38.6–54.7), I2 =  52.0%] and lambda [two studies, 188 patients, WMD 50.3 (95% CI 21.4–79.3), I2 = 95.1%] light chain levels. Conclusion Current evidence from RCTs and OBSs suggests HCO dialysis is able to reduce serum free light chains but makes no significant improvement in all-cause mortality and renal outcomes compared with conventional HD for patients with myeloma cast nephropathy. However, there is a trend towards better renal outcomes with the use of HCO dialysis. The lack of long-term data and the small sample sizes of the included studies limit this analysis. Therefore further large-scale RCTs with longer follow-up are needed to assess the effect of HCO dialysis on clinical outcomes in patients with myeloma cast nephropathy.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Blanca Tarragon ◽  
Nan Ye ◽  
Martin Gallagher ◽  
Shaundeep Sen ◽  
Jose' M Portoles ◽  
...  

Abstract Background and Aims The incidence of multiple myeloma (MM) is increasing. Abnormal secretion of serum free light chains (sFLC) can lead to cast nephropathy and severe acute kidney injury (AKI) requiring haemodialysis (HD), which is associated with increased morbidity and mortality. High cut-off (HCO) HD membranes demonstrate better sFLC clearance. However, their role in all-cause mortality and renal recovery remains uncertain. Method A systematic review and meta-analysis was performed examining all randomized controlled trials (RCTs) and observational studies assessing the effect of high cut-off HD compared to conventional HD on clinical outcomes of patients with MM complicated by cast nephropathy induced-severe AKI. Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until September 2019. The primary outcome was all-cause mortality at the end of the study. The secondary outcomes included all-cause mortality at 12 months, haemodialysis independence at 3, 6 and 12 months, biopsy-proven haematologic responses at 90 days and sFLC (kappa and lambda) reduction. Random effect models were used to pool relative risks (RR) with 95% confidence intervals (CIs) for individual studies. Results The search identified 5 studies including 276 patients with a mean follow-up of 18.7 months. There were 2 RCTs and 3 retrospective cohort studies. Compared with patients treated with conventional HD, patients on HCO dialysis did not show survival benefits at 12 months (4 studies, 186 patients, RR 0.79; 95% CI 0.46-1.36), or at the end of the study (5 studies, 276 patients, RR 0.86; 95% CI 0.60-1.25). Although survival benefits at the end of study (3 studies, 88 patients, RR 0.64; 95% CI 0.45-0.90) were seen in observational studies, no differences in all-cause mortality was seen in RCTs (2 studies, 188 patients, RR 1.31; 95% CI 0.50-3.46). Likewise, although the pooled data from the observational studies demonstrated significantly higher rates of HD independence at 90 days (2 trials, 78 patients, RR 2.23; 95% CI 1.09-4.55), this difference disappeared when the data from RCTs were included to the analysis (4 studies, 266 patients, RR 1.28; 95% CI 0.95-1.73).  There was no difference in HD Independence at 6 months (2 studies, 188 patients, RR 1.19; 95% CI 0.68-2.06), and 12 months (2 studies, 188 patients, RR 1.14; 95% CI 0.58-2.26) between these two therapies. Patients receiving HCO dialysis, however, had significantly better biopsy-proven haematologic response at 90 days by 40% (3 studies, 176 patients, RR 1,40; 95% CI 1.13-1.74) and a significantly higher kappa light chain reduction (2 studies, 188 patients, standardized mean difference (SMD) 2.37; 95% CI 1.99-2.75; I2 = 0%). Overall, the majority of the studies were of suboptimal quality and underpowered. Conclusion Current evidence from RCTs and observational studies suggest HCO dialysis provides haematological benefits but makes no significant improvement in all-cause mortality and renal outcomes, compared to conventional HD for patients with multiple myeloma associated cast nephropathy. However, there is a trend towards better renal outcomes, therefore further large-scale RCTs are needed to assess the effect of HCO dialysis on clinical outcomes in patients with multiple myeloma complicated by cast-nephropathy.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Konstantin Vishnevskii ◽  
Olga Domashenko

Abstract Background and Aims The myeloma cast nephropathy is largely associated with the production of intact immunoglobulin and free light chains (FLC) by a plasma cells monoclone. The use of high-flux hemodiafiltration (HDF) contributes to a decrease in the concentration of FLC. However, it is not always possible to achieve the required substitute volume with acute kidney injury (AKI) emergency treatment. An alternative to HDF could be the usage of membranes with a medium cut-off (expanded hemodialysis (HD), Expanded HD). The aim of this study was to compare the degree of reduction in FLC concentration using conventional HD, HDF and Expanded HD. Method The study includes patients with newly diagnosed multiple myeloma who presented indications for HD therapy start. Procedures were performed on a daily basis from the moment when indications for HD therapy were identified. The duration of the first three procedures was 2 hours. Consistently for each patient the first procedure was carried out using a standard low-flow filter, the second - using a high-flow dialyzer and HDF (substitute volume 9 liters for 2 hours), the third - using a Theranova 400 filter (Baxter, Germany). The concentrations of FLC (kappa and lambda) and albumin were determined every 30 minutes of each treatment. Chemotherapy was prescribed according to the local clinical recommendations in combination with the ongoing renal replacement therapy. Results The study included 7 patients with cast nephropathy, mean age 68±8 years. Average concentration before treatment: kappa FLC 876±727 μg/ml (norm 3.25-15.81 μg/ml), lambda FLK 84±112 μg/ml (norm 3.23-28.05 μg/ml), albumin 34±1 g/l (norm 40-50 g/l). After 2 hours of treatment, there was a decrease in kappa FLC concentration with HDF (-34±33%, p=0.01) and with Expanded HD (-31±12%, p<0.001), but not with conventional HD (-1±7, p=0.79, Fig 1). The lambda FLC concentration also decreased with HDF (-41±29%, p=0.01) and with Expanded HD (-28±22%, p=0.01), but not with conventional HD (-3±12, p=0.65, Fig 2). Albumin concentrations did not change significantly with any of the treatments. Conclusion Expanded HD, as well as high-flow HDF, helps to reduce the FLC concentration in patients with cast nephropathy without loss of albumin, which may have a positive effect on the multiple myeloma prognosis. Further studies are needed regarding possibilities of using Expanded HD in the complex therapy for patients with AKI in myeloma cast nephropathy.


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Eleni Papoutsi ◽  
Vassilis G. Giannakoulis ◽  
Eleni Xourgia ◽  
Christina Routsi ◽  
Anastasia Kotanidou ◽  
...  

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.


2021 ◽  
pp. 1-8
Author(s):  
Huiyang Li ◽  
Peng Zhou ◽  
Yikai Zhao ◽  
Huaichun Ni ◽  
Xinping Luo ◽  
...  

Abstract Objective: The aim of this meta-analysis was to investigate the association between malnutrition assessed by the controlling nutritional status (CONUT) score and all-cause mortality in patients with heart failure. Design: Systematic review and meta-analysis. Settings: A comprehensively literature search of PubMed and Embase databases was performed until 30 November 2020. Studies reporting the utility of CONUT score in prediction of all-cause mortality among patients with heart failure were eligible. Patients with a CONUT score ≥2 are grouped as malnourished. Predictive values of the CONUT score were summarized by pooling the multivariable-adjusted risk ratios (RR) with 95 % CI for the malnourished v. normal nutritional status or per point CONUT score increase. Participants: Ten studies involving 5196 patients with heart failure. Results: Malnourished patients with heart failure conferred a higher risk of all-cause mortality (RR 1·92; 95 % CI 1·58, 2·34) compared with the normal nutritional status. Subgroup analysis showed the malnourished patients with heart failure had an increased risk of in-hospital mortality (RR 1·78; 95 % CI 1·29, 2·46) and follow-up mortality (RR 2·01; 95 % CI 1·58, 2·57). Moreover, per point increase in CONUT score significantly increased 16% risk of all-cause mortality during the follow-up. Conclusions: Malnutrition defined by the CONUT score is an independent predictor of all-cause mortality in patients with heart failure. Assessment of nutritional status using CONUT score would be helpful for improving risk stratification of heart failure.


Author(s):  
Ahmad Hazem ◽  
Sunita Sharma ◽  
Amit Sharma ◽  
Cameron Leitch ◽  
Roopalakshmi Sharadanant ◽  
...  

Importance: Up to 10% of patients with acute myocardial infarction (AMI) have right bundle branch block (RBBB), and RBBB has been associated with a higher risk of mortality. We performed a systematic review and meta-analysis to determine the prognostic significance of RBBB for patients with AMI. Acute coronary syndrome (ACS) Data Sources: We have systematically searched Ovid, Scopus and Web of Science through January 2014. Study Selection: Reviewers working independently and in duplicate screened all eligible abstracts, selecting studies that described all-cause mortality or cardiovascular death in patients with RBBB and suspected ACS. We excluded studies that reported unadjusted outcomes. Knowledge synthesis: We pooled risk ratio with hazard ratio in studies reporting those outcomes. When reported, odds ratio was converted into risk ratio using reported event rate in each study’s unexposed -read: non RBBB- group. Main Outcomes: All-cause mortality and cardiovascular mortality (death). Results: Eighteen studies were found that reported eligible data. All were observational studies, involving over 89,000 patients. In short-term follow up (up to 30 days), RBBB on presentation was associated with higher all-cause mortality rate, compared to patients without RBBB (RR 2.23, 95% CI 1.76-2.82). There was a trend for higher mortality at long-term follow up (range: 6 months-16 years) that did not reach statistical significance (RR 1.45, 95% CI 0.93-2.25). Figure-1 demonstrates the forest plot. Risk of bias was assessed with the Newcastle-Ottawa scale and majority of included studied were deemed moderate to high quality. Conclusion and Relevance: RBBB is associated with a more than 2-fold higher risk of all-cause mortality in patients with AMI at 30 days follow up. Patients with AMI and RBBB represent a high risk group for adverse outcomes. A sentence on the differential findings for new vs. old RBBB and association with outcomes could follow here.


2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Chitra Punjabi ◽  
Vivian Tien ◽  
Lina Meng ◽  
Stan Deresinski ◽  
Marisa Holubar

Abstract Background Using published data, we sought to compare outcomes in patients transitioned to either oral fluoroquinolones (FQs) or trimethoprim-sulfamethoxazole (TMP-SMX) vs ß-lactams (BLs) after an initial intravenous (IV) course for gram-negative rod (GNR) bacteremia. Methods We conducted a systematic review of PubMed and EMBASE and published IDWeek abstracts. We included studies that reported all-cause mortality and/or infection recurrence in patients transitioned to oral FQ/TMP-SMX and BLs. Results Eight retrospective studies met inclusion criteria with data for 2289 patients, of whom 65% were transitioned to oral FQs, 7.7% to TMP-SMX, and 27.2% to BLs. Follow-up periods ranged from 21 to 90 days. All-cause mortality was not significantly different between patients transitioned to either FQ/TMP-SMX or BLs (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69–1.87). Overall recurrence of infection, either bacteremia or the primary site, occurred more frequently in patients transitioned to oral BLs vs FQs (OR, 2.05; 95% CI, 1.17–3.61). Analysis limited to recurrent bacteremia was similarly suggestive, although limited by small numbers (OR, 2.15; 95% CI, 0.93–4.99). However, based on known pharmacokinetics/pharmacodynamics, prescribed ß-lactam dosing regimens were frequently suboptimal. Conclusions In the step-down IV to oral treatment of GNR bacteremia, we found insufficient data regarding outcomes after oral TMP-SMX; however, selection of an FQ over commonly utilized ß-lactam regimens may reduce chances of infection recurrence. Although this may be a class effect, it may simply be the result of inadequate dosing of ß-lactams. Additional investigations are warranted to determine outcomes with TMP-SMX and optimized oral ß-lactam dosing regimens.


2019 ◽  
Vol 26 (5) ◽  
pp. 600-612 ◽  
Author(s):  
Krystal Dinh ◽  
Alexandra M. Limmer ◽  
Sharath C. V. Paravastu ◽  
Shannon D. Thomas ◽  
Michael H. Bennett ◽  
...  

Purpose: To report the risk of all-cause mortality in patients who underwent dialysis access treatment using paclitaxel-coated devices compared with percutaneous transluminal angioplasty (PTA) with an uncoated balloon. Materials and Methods: A systematic review and meta-analysis of randomized controlled trials were performed to investigate the mortality outcomes associated with paclitaxel-coated devices in the treatment of patients with a failing dialysis access (last search date February 28, 2019). The primary endpoint was all-cause mortality. This analysis included 8 studies comparing paclitaxel-coated balloon (PCB) angioplasty (n=327) and PTA (n=331) in the treatment of failing dialysis access. None investigated paclitaxel-coated stents. Mortality data were pooled using a random effects model. Statistical heterogeneity was evaluated with a chi-square test and the I2 statistic. Summary statistics are expressed as relative risk ratios (RR) with a 95% confidence interval (CI). Results: At the pooled mean follow-up of 13.5 months (median 12, range 6–24) all-cause mortality was similar in the PCB group (13.8%) compared with PTA (11.2%; RR 1.26, 95% CI 0.85 to 1.89, p=0.25; I2=0%). Subgroup analysis, stratified according to length of follow-up, confirmed that there were no statistically significant differences in mortality at short- and midterm follow-up [6-month (8 studies): 5.2% vs 4.8%, RR 1.24, 95% CI 0.62 to 2.47, p=0.55; 12-month (6 studies): 6.3% vs 6.0%, RR 1.06, 95% CI 0.43 to 2.63, p=0.90; and 24-month (3 studies): 19.0% vs 13.5%, RR 1.38, 95% CI 0.90 to 2.12, p=0.14). Conclusion: The analysis found no difference in short- to midterm mortality among patients treated with a drug-coated balloon compared with PTA. With proven benefit and no evidence of harm, the authors recommend ongoing use of PCB for the failing dialysis access.


2019 ◽  
Vol 180 (4) ◽  
pp. 243-255 ◽  
Author(s):  
Guodong Xu ◽  
Dingyun You ◽  
Liping Wong ◽  
Donghui Duan ◽  
Fanqian Kong ◽  
...  

Objective Previous studies have shown sex-specific differences in all-cause and CHD mortality in type 2 diabetes. We performed a systematic review and meta-analysis to provide a global picture of the estimated influence of type 2 diabetes on the risk of all-cause and CHD mortality in women vs men. Methods We systematically searched PubMed, EMBASE and Web of Science for studies published from their starting dates to Aug 7, 2018. The sex-specific hazard ratios (HRs) and their pooled ratio (women vs men) of all-cause and CHD mortality associated with type 2 diabetes were obtained through an inverse variance-weighted random-effects meta-analysis. Subgroup analyses were used to explore the potential sources of heterogeneity. Results The 35 analyzed prospective cohort studies included 2 314 292 individuals, among whom 254 038 all-cause deaths occurred. The pooled women vs men ratio of the HRs for all-cause and CHD mortality were 1.17 (95% CI: 1.12–1.23, I2 = 81.6%) and 1.97 (95% CI: 1.49–2.61, I2 = 86.4%), respectively. The pooled estimate of the HR for all-cause mortality was approximately 1.30 in articles in which the duration of follow-up was longer than 10 years and 1.10 in articles in which the duration of follow-up was less than 10 years. The pooled HRs for all-cause mortality in patients with type 2 diabetes was 2.33 (95% CI: 2.02–2.69) in women and 1.91 (95% CI: 1.72–2.12) in men, compared with their healthy counterparts. Conclusions The effect of diabetes on all-cause and CHD mortality is approximately 17 and 97% greater, respectively, for women than for men.


2020 ◽  
Author(s):  
Innocent G Asiimwe ◽  
Sudeep Pushpakom ◽  
Richard M Turner ◽  
Ruwanthi Kolamunnage-Dona ◽  
Andrea Jorgensen ◽  
...  

ABSTRACTOBJECTIVETo continually evaluate the rapidly evolving evidence base on the role of cardiovascular drugs in COVID-19 clinical outcomes (susceptibility to infection, hospitalization, hospitalization length, disease severity, and all-cause mortality).DESIGNLiving systematic review and meta-analysis.DATA SOURCESEligible publications identified from >500 databases indexed through 31st July 2020 and additional studies from reference lists, with planned continual surveillance for at least two years.STUDY SELECTIONObservational and interventional studies that report on the association between cardiovascular drugs and COVID-19 clinical outcomes.DATA EXTRACTIONSingle-reviewer extraction and quality evaluation (using ROBINS-I), with half the records independently extracted and evaluated by a second reviewer.RESULTSOf 23,427 titles screened, 175 studies were included in the quantitative synthesis. The most reported drug classes were angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) with ACEI/ARB exposure being associated with higher odds of testing positive for COVID-19 (pooled unadjusted OR 1.15, 95% CI 1.02 to 1.30). Among patients with COVID-19, unadjusted estimates showed that ACEI/ARB exposure was associated with being hospitalized (OR 2.25, 1.70 to 2.98) and having severe disease (OR 1.50, 1.27 to 1.77) but not with the length of hospitalization (mean difference −0.45, −1.33 to 0.43 days) or all-cause mortality (OR 1.25, CI 0.98 to 1.58). However, after adjustment, ACEI/ARB exposure was not associated with testing positive for COVID-19 (pooled adjusted OR 1.01, 0.93 to 1.10), being hospitalized (OR 1.16, 0.80 to 1.68), having severe disease (1.04, 0.76 to 1.42), or all-cause mortality (0.86, 0.64 to 1.15). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with being hospitalized (OR 0.84, 0.58 to 1.22), disease severity (OR 0.88, 0.68 to 1.14) or all-cause mortality (OR 0.77, 0.54 to 1.12) while it decreased the length of hospitalization (mean difference −0.71, −1.11 to −0.30 days). After adjusting for relevant covariates, other cardiovascular drug classes were mostly not found to be associated with poor COVID-19 clinical outcomes. However, the validity of these findings is limited by a high level of heterogeneity in terms of effect sizes and a serious risk of bias, mainly due to confounding in the included studies.CONCLUSIONOur comprehensive review shows that ACEI/ARB exposure is associated with COVID-19 outcomes such as susceptibility to infection, severity, and hospitalization in unadjusted analyses. However, after adjusting for potential confounding factors, this association is not evident. Patients on cardiovascular drugs should continue taking their medications as currently recommended. Higher quality evidence in the form of randomized controlled trials will be needed to determine any adverse or beneficial effects of cardiovascular drugs.PRIMARY FUNDING SOURCENoneSYSTEMATIC REVIEW REGISTRATIONPROSPERO (CRD42020191283)


Sign in / Sign up

Export Citation Format

Share Document